Impact of Hypocalcemia on the Prognosis of Patients with Acute Myocarditis.

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.

Predictive Value of Myocardial injury in Patients with COVID-19 Admitted to a Quaternary Hospital in the City of Rio de Janeiro

Abstract Background In Brazil the factors involved in the risk of death in patients with COVID-19 have not been well established. Objective To analyze whether elevations of high-sensitivity troponin I (hTnI) levels influence the mortality of patients with COVID-19. Methods Clinical and laboratory characteristics of hospitalized patients with COVID-19 were collected upon hospital admission. Univariate and binary logistic regression analyzes were performed to assess the factors that influence mortality. P-value<0.05 was considered significant. Results This study analyzed192 patients who received hospital admission between March 16 and June 2, 2020 and who were discharged or died by July 2, 2020. The mean age was 70±15 years, 80 (41.7%) of whom were women. In comparison to those who were discharged, the 54 (28.1%) who died were older (79±12 vs 66±15years; P=0.004), and with a higher Charlson´s index (5±2 vs 3±2; P=0.027). More patients, aged≥60years (P <0.0001), Charlson´s index>1 (P=0.004), lung injury>50% in chest computed tomography (P=0.011), with previous coronary artery disease (P=0.037), hypertension (P=0.033), stroke (P=0.008), heart failure (P=0.002), lymphocytopenia (P=0.024), high D-dimer (P=0.024), high INR (P=0.003), hTnI (P<0.0001), high creatinine (P<0.0001), invasive mechanical ventilation (P<0.0001), renal replacement therapy (P<0.0001), vasoactive amine (P<0.0001), and transfer to the ICU (P=0.001), died when compared to those who were discharged. In logistic regression analysis, elevated hTnI levels (OR=9.504; 95% CI=1.281-70.528; P=0.028) upon admission, and the need for mechanical ventilation during hospitalization (OR=46.691; 95% CI=2.360-923.706; P=0.012) increased the chance of in-hospital mortality. Conclusion This study suggests that in COVID-19 disease, myocardial injury upon hospital admission is a harbinger of poor prognosis.

Cardiovascular Risk Assessment after COVID-19 Infection before Resuming Sports Activities - Practical Flowchart and Meta-Analysis

Abstract Background: The risk of sports-related sudden cardiac arrest after COVID-19 infection can be a serious problem. There is an urgent need for evidence-based criteria to ensure patient safety before resuming exercise. Objective: To estimate the pooled prevalence of acute myocardial injury caused by COVID-19 and to provide an easy-to-use cardiovascular risk assessment toolkit prior to resuming sports activities after COVID-19 infection. Methods: We searched the Medline and Cochrane databases for articles on the prevalence of acute myocardial injury associated with COVID-19 infection. The pooled prevalence of acute myocardial injury was calculated for hospitalized patients treated in different settings (non-intensive care unit [ICU], ICU, overall hospitalization, and non-survivors). Statistical significance was accepted for p values <0.05. We propose a practical flowchart to assess the cardiovascular risk of individuals who recovered from COVID-19 before resuming sports activities. Results: A total of 20 studies (6,573 patients) were included. The overall pooled prevalence of acute myocardial injury in hospitalized patients was 21.7% (95% CI 17.3-26.5%). The non-ICU setting had the lowest prevalence (9.5%, 95% CI 1.5-23.4%), followed by the ICU setting (44.9%, 95% CI 27.7-62.8%), and the cohort of non-survivors (57.7% with 95% CI 38.5-75.7%). We provide an approach to assess cardiovascular risk based on the prevalence of acute myocardial injury in each setting. Conclusions: Acute myocardial injury is frequent and associated with more severe disease and hospital admissions. Cardiac involvement could be a potential trigger for exercise-induced clinical complications after COVID-19 infection. We created a toolkit to assist with clinical decision-making prior to resuming sports activities after COVID-19 infection.

Cardiac MRI in patients with COVID-19 infection.

OBJECTIVE: COVID-19 infection is a systemic disease with various cardiovascular symptoms and complications. Cardiac MRI with late gadolinium enhancement is the modality of choice for the assessment of myocardial involvement. T1 and T2 mapping can increase diagnostic accuracy and improve further management. Our study aimed to evaluate the different aspects of myocardial damage in cases of COVID-19 infection using cardiac MRI. METHODS: This descriptive retrospective study included 86 cases, with a history of COVID-19 infection confirmed by positive RT-PCR, who met the inclusion criteria. Patients had progressive chest pain or dyspnoea with a suspected underlying cardiac cause, either by an abnormal electrocardiogram or elevated troponin levels. Cardiac MRI was performed with late contrast-enhanced (LGE) imaging, followed by T1 and T2 mapping. RESULTS: Twenty-four patients have elevated hsTnT with a median hsTnT value of 133 ng/L (IQR: 102 to 159 ng/L); normal value < 14 ng/L. Other sixty-two patients showed elevated hsTnI with a median hsTnI value of 1637 ng/L (IQR: 1340 to 2540 ng/L); normal value < 40 ng/L. CMR showed 52 patients with acute myocarditis, 23 with Takotsubo cardiomyopathy, and 11 with myocardial infarction. Invasive coronary angiography was performed only in selected patients. CONCLUSION: Different COVID-19-related cardiac injuries may cause similar clinical symptoms. Cardiac MRI is the modality of choice to differentiate between the different types of myocardial injury such as Takotsubo cardiomyopathy and infection-related cardiomyopathy or even acute coronary syndrome secondary to vasculitis or oxygen-demand mismatch. KEY POINTS: • It is essential to detect early COVID-related cardiac injury using different cardiac biomarkers and cardiac imaging, as it has a significant impact on patient management and outcome. • Cardiac MRI is the modality of choice to differentiate between the different aspects of COVID-related myocardial injury.

Cardiac magnetic resonance findings in acute and post-acute COVID-19 patients with suspected myocarditis.

INTRODUCTION: Cardiac injury is commonly reported in COVID-19 patients, resulting associated to pre-existing cardiovascular disease, disease severity, and unfavorable outcome. Aim is to report cardiac magnetic resonance (CMR) findings in patients with myocarditis-like syndrome during the acute phase of SARS-CoV-2 infection (AMCovS) and post-acute phase (cPACS). METHODS: Between September 2020 and January 2022, 39 consecutive patients (24 males, 58%) were referred to our department to perform a CMR for the suspicion of myocarditis related to AMCovS (n = 17) and cPACS (n = 22) at multimodality evaluation (clinical, laboratory, ECG, and echocardiography). CMR was performed for the assessment of volume, function, edema and fibrosis with standard sequences and mapping techniques. CMR diagnosis and the extension and amount of CMR alterations were recorded. RESULTS: Patients with suspected myocarditis in acute and post-COVID settings were mainly men (10 (59%) and 12 (54.5%), respectively) with older age in AMCovS (58 [48-64]) compared to cPACS (38 [26-53]). Myocarditis was confirmed by CMR in most of cases: 53% of AMCovS and 50% of cPACS with negligible LGE burden (3 [IQR, 1-5] % and 2 [IQR, 1-4] %, respectively). Myocardial infarction was identified in 4/17 (24%) patients with AMCovS. Cardiomyopathies were identified in 12% (3/17) and 27% (6/22) of patients with AMCovS and cPACS, including DCM, HCM and mitral valve prolapse. CONCLUSIONS: In patients with acute and post-acute COVID-19 related suspected myocarditis, CMR improves diagnostic accuracy characterizing ischemic and non-ischemic injury and unraveling subclinical cardiomyopathies.

Cardiac magnetic resonance -detected myocardial injury is not associated with long-term symptoms in patients hospitalized due to COVID-19.

BACKGROUND: Long-term symptoms are frequent after coronavirus disease 2019 (COVID-19). We studied the prevalence of post-acute myocardial scar on cardiac magnetic resonance imaging (CMR) in patients hospitalized due to COVID-19 and its association with long-term symptoms. MATERIALS AND METHODS: In this prospective observational single-center study, 95 formerly hospitalized COVID-19 patients underwent CMR imaging at the median of 9 months after acute COVID-19. In addition, 43 control subjects were imaged. Myocardial scar characteristic of myocardial infarction or myocarditis were noted from late gadolinium enhancement images (LGE). Patient symptoms were screened using a questionnaire. Data are presented as mean ± standard deviation or median (interquartile range). RESULTS: The presence of any LGE was higher in COVID-19 patients (66% vs. 37%, p<0.01) as was the presence of LGE suggestive of previous myocarditis (29% vs. 9%, p = 0.01). The prevalence of ischemic scar was comparable (8% vs. 2%, p = 0.13). Only two COVID-19 patients (7%) had myocarditis scar combined with left ventricular dysfunction (EF <50%). Myocardial edema was not detected in any participant. The need for intensive care unit (ICU) treatment during initial hospitalization was comparable in patients with and without myocarditis scar (47% vs. 67%, p = 0.44). Dyspnea, chest pain, and arrhythmias were prevalent in COVID-19 patients at follow-up (64%, 31%, and 41%, respectively) but not associated with myocarditis scar on CMR. CONCLUSIONS: Myocardial scar suggestive of possible previous myocarditis was detected in almost one-third of hospital-treated COVID-19 patients. It was not associated with the need for ICU treatment, greater symptomatic burden, or ventricular dysfunction at 9 months follow-up. Thus, post-acute myocarditis scar on COVID-19 patients seems to be a subclinical imaging finding and does not commonly require further clinical evaluation.

A distinct septal pattern of late gadolinium enhancement specific for COVID-induced myocarditis: A multicenter cardiovascular magnetic resonance study.

BACKGROUND: COVID-19 is a great medical challenge as it provokes acute respiratory distress and has pulmonary manifestations and cardiovascular (CV) consequences. AIMS: This study compared cardiac injury in COVID-19 myocarditis patients with non-COVID-19 myocarditis patients. METHODS: Patients who recovered from COVID-19 were scheduled for cardiovascular magnetic resonance (CMR) owing to clinical myocarditis suspicion. The retrospective non-COVID-19 myocarditis (2018-2019) group was enrolled (n = 221 patients). All patients underwent contrast-enhanced CMR, the conventional myocarditis protocol, and late gadolinium enhancement (LGE). The COVID study group included 552 patients at a mean (standard deviation [SD]) age of 45.9 (12.6) years. RESULTS: CMR assessment confirmed myocarditis-like LGE in 46% of the cases (68.5% of the segments with LGE <25% transmural extent), left ventricular (LV) dilatation in 10%, and systolic dysfunction in 16% of cases. The COVID-19 myocarditis group showed a smaller median (interquartile range [IQR]) LV LGE (4.4% [2.9%-8.1%] vs. 5.9% [4.4%-11.8%]; P <0.001), lower LV end-diastolic volume (144.6 [125.5-178] ml vs. 162.8 [136.6-194] ml; P <0.001), limited functional consequence (left ventricular ejection fraction, 59% [54.1%-65%] vs. 58% [52%-63%]; P = 0.01), and a higher rate of pericarditis (13.6% vs. 6%; P = 0.03) compared to non-COVID-19 myocarditis. The COVID-19-induced injury was more frequent in septal segments (2, 3, 14), and non-COVID-19 myocarditis showed higher affinity to lateral wall segments (P <0.01). Neither obesity nor age was associated with LV injury or remodeling in subjects with COVID-19 myocarditis. CONCLUSIONS: COVID-19-induced myocarditis is associated with minor LV injury with a significantly more frequent septal pattern and a higher pericarditis rate than non-COVID-19 myocarditis.

Short term outcome of myocarditis and pericarditis following COVID-19 vaccines: a cardiac magnetic resonance imaging study.

To evaluate clinical and cardiac magnetic resonance (CMR) short-term follow-up (FU) in patients with vaccine-associated myocarditis, pericarditis or myo-pericarditis (VAMP) following COVID-19 vaccination. We retrospectively analyzed 44 patients (2 women, mean age: 31.7 ± 15.1 years) with clinical and CMR manifestations of VAMP, recruited from 13 large tertiary national centers. Inclusion criteria were troponin raise, interval between the last vaccination dose and onset of symptoms < 25 days and symptoms-to-CMR < 20 days. 29/44 patients underwent a short-term FU-CMR with a median time of 3.3 months. Ventricular volumes and CMR findings of cardiac injury were collected in all exams. Mean interval between the last vaccination dose and the onset of symptoms was 6.2 ± 5.6 days. 30/44 patients received a vaccination with Comirnaty, 12/44 with Spikevax, 1/44 with Vaxzevria and 1/44 with Janssen (18 after the first dose of vaccine, 20 after the second and 6 after the "booster" dose). Chest pain was the most frequent symptom (41/44), followed by fever (29/44), myalgia (17/44), dyspnea (13/44) and palpitations (11/44). At baseline, left ventricular ejection fraction (LV-EF) was reduced in 7 patients; wall motion abnormalities have been detected in 10. Myocardial edema was found in 35 (79.5%) and LGE in 40 (90.9%) patients. Clinical FU revealed symptoms persistence in 8/44 patients. At FU-CMR, LV-EF was reduced only in 2 patients, myocardial edema was present in 8/29 patients and LGE in 26/29. VAMPs appear to have a mild clinical presentation, with self-limiting course and resolution of CMR signs of active inflammation at short-term follow-up in most of the cases.

Incidence and risk factors of myocarditis in hospitalized patients with COVID-19.

Myocarditis as cardiac involvement in coronavirus disease 2019 (COVID-19)-infection is well known. Real-world data about incidence in hospitalized COVID-19-patients and risk factors for myocarditis in COVID-19-patients are sparse. We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19-diagnosis in Germany in 2020 and stratified them for myocarditis. Overall, 176 137 hospitalizations (52.3% males, 53.6% aged ≥70 years) with confirmed COVID-19-infection were coded in Germany in 2020 and among them, 226 (0.01%) had myocarditis (incidence: 1.28 per 1000 hospitalization-cases). Absolute numbers of myocarditis increased, while relative numbers decreased with age. COVID-19-patients with myocarditis were younger (64.0 [IQR: 43.0/78.0] vs. 71.0 [56.0/82.0], p < 0.001). In-hospital case-fatality was 1.3-fold higher in COVID-19-patients with than without myocarditis (24.3% vs. 18.9%, p = 0.012). Myocarditis was independently associated with increased case-fatality (OR: 1.89 [95% CI: 1.33-2.67], p < 0.001). Independent risk factors for myocarditis were age <70 years (OR: 2.36 [95% CI: 1.72-3.24], p < 0.001), male sex (1.68 [95% CI: 1.28-2.23], p < 0.001), pneumonia (OR: 1.77 [95% CI: 1.30-2.42], p < 0.001), and multisystemic inflammatory COVID-19-infection (OR: 10.73 [95% CI: 5.39-21.39], p < 0.001). The incidence of myocarditis in hospitalized COVID-19-patients in Germany was 1.28 cases per 1000 hospitalizations in 2020. Risk factors for myocarditis in COVID-19 were young age, male sex, pneumonia, and multisystemic inflammatory COVID-19-infection. Myocarditis was independently associated with increased case-fatality.

Cardiac manifestations in children with the multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 infection: Systematic review and meta-analysis.

According to the World Health Organisation, as of October 2022, there have been 55,560,329 reported cases of SARS-COV-2 in patients under 19 years old. It is estimated that about 0.06% of these patients may develop MIS-C, representing more than 2 million children worldwide. This systematic review and meta-analysis examined the pooled prevalence of cardiovascular manifestation and cardiac complications in children hospitalised with MIS-C. The PROSPERO register number is CRD42022327212. We included case-report studies, case-control studies, cohort studies, and cross-sectional studies, as well as clinical trials or studies describing cardiac manifestations of MIS-C and its sequelae in a paediatric population. Initially, 285 studies were selected, but there were 154 duplicates, and 81 were excluded because they did not fit the eligibility criteria. Thus, 50 studies were selected for review, and 30 were included in the meta-analysis. A total sample size of 1445 children was included. The combined prevalence of myocarditis or pericarditis was 34.3% (95% CI: 25.0%-44.2%). The combined prevalence for echocardiogram anomalies was 40.8% (95% CI: 30.5%-51.5%), that of Kawasaki disease presentation was 14.8% (95% CI: 7.5%-23.7%), and that of coronary dilation was 15.2% (95% CI: 11.0%-19.8%). The rate of electrocardiogram anomalies was 5.3% (95% CI: 0.8%-12.3%), and the mortality rate was 0.5% (CI 95%: 0%-1.2%). Furthermore, 186 children still had complications at discharge, with a combined prevalence of such long-lasting manifestations of 9.3% (95% CI: 5.6%-13.7%). Studies that assess whether these children will have an increased cardiovascular risk with a greater chance of acute myocardial infarction, arrhythmias, or thrombosis will be essential for healthcare planning.

A case of fatal multi-organ inflammation following COVID-19 vaccination.

A 14-year-old Japanese girl died unexpectedly 2 days after receiving the third dose of the BNT1262b2 mRNA COVID-19 vaccine. Autopsy findings showed congestive edema of the lungs, T-cell lymphocytic and macrophage infiltration in the lungs, pericardium, and myocardium of the left atria and left ventricle, liver, kidneys, stomach, duodenum, bladder, and diaphragm. Since there was no preceding infection, allergy, or drug toxicity exposure, the patient was diagnosed with post-vaccination pneumonia, myopericarditis, hepatitis, nephritis, gastroenteritis, cystitis, and myositis. Although neither type of inflammation is fatal by itself, arrhythmia is reported to be the most common cause of death in patients with atrial myopericarditis. In the present case, arrhythmia of atrial origin was assumed as the cause of cardiac failure and death. In sudden post-vaccination deaths, aggressive autopsy systemic search and histological examination involving extensive sectioning of the heart, including the atrium, are indispensable.

Arrhythmia occurring as the sole presenting feature in Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection is observed to be associated with several cardiac complications. Cardiac arrhythmias are frequently observed in critically ill patients and are usually associated with myocarditis. We report two patients with Covid-19, in whom serious arrhythmias were the sole presenting feature, in the absence of any of the known manifestations of the disease. Further research is required into this yet unknown mechanism of the effect of Covid-19 on the conduction system. Thus, managing patients with acute-onset arrhythmias of unexplained aetiology, even when they present without known clinical features of Covid-19, should be done with care.

10-year survival outcome after clinically suspected acute myocarditis in adults: A nationwide study in the pre-COVID-19 era.

BACKGROUND: Clinical courses of acute myocarditis are heterogeneous in populations and geographic regions. There is a dearth of long-term outcomes data for acute myocarditis prior to the coronavirus disease pandemic, particularly in the older and female population. This study aimed to provide the nationwide epidemiologic approximates of clinically suspected acute myocarditis across adults of all ages over the long term. METHODS: From the nationwide governmental health insurance database, a retrospective cohort comprised all patients aged 20-79 who were hospitalized for clinically suspected acute myocarditis without underlying cardiac diseases from 2006 to 2018. The complicated phenotype was defined as requiring hemodynamic or major organ support. Over 10 years, all-cause mortality and index event-driven excess mortality were evaluated according to young-adult (20-39 years), mid-life (40-59 years), and older-adult (60-79 years) age groups. RESULTS: Among 2,988 patients (51.0±16.9 years, 46.2% women), 362 (12.1%) were of complicated phenotype. Of these, 163 (45.0%) had died within 1 month. All-cause death at 30 days occurred in 40 (4.7%), 52 (4.8%), and 105 (10.0%) patients in the young-adult, mid-life, and older-adult groups, respectively. For 10 years of follow-up, all-cause death occurred in 762 (25.5%). Even in young adult patients with non-complicated phenotypes, excess mortality remained higher compared to the general population. CONCLUSION: In hospitalized patients with clinically suspected acute myocarditis, short-term mortality is high both in young and older adults, particularly those with comorbidities and severe clinical presentation. Furthermore, excess mortality remains high for at least 10 years after index hospitalization in young adults.

COVID-19 Associated Myocarditis Clinical Outcomes among Hospitalized Patients in the United States: A Propensity Matched Analysis of National Inpatient Sample.

Coronavirus-19 (COVID-19), preliminarily a respiratory virus, can affect multiple organs, including the heart. Myocarditis is a well-known complication among COVID-19 infections, with limited large-scale studies evaluating outcomes associated with COVID-19-related Myocarditis. We used the National Inpatient Sample (NIS) database to compare COVID-19 patients with and without Myocarditis. A total of 1,659,040 patients were included in the study: COVID-19 with Myocarditis (n = 6,455, 0.4%) and COVID-19 without Myocarditis (n = 1,652,585, 99.6%). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation, vasopressor use, sudden cardiac arrest, cardiogenic shock, acute kidney injury requiring hemodialysis, length of stay, health care utilization costs, and disposition. We conducted a secondary analysis with propensity matching to confirm results obtained by traditional multivariate analysis. COVID-19 patients with Myocarditis had significantly higher in-hospital mortality compared to COVID-19 patients without Myocarditis (30.5% vs. 13.1%, adjusted OR: 3 [95% CI 2.1-4.2], p < 0.001). This cohort also had significantly increased cardiogenic shock, acute kidney injury requiring hemodialysis, sudden cardiac death, required more mechanical ventilation and vasopressor support and higher hospitalization cost. Vaccination and more research for treatment strategies will be critical for reducing worse outcomes in patients with COVID-19-related Myocarditis.

A Successful Case of Cardiac Arrest due to Acute Myocarditis with COVID-19: 120 Minutes on Manual Cardiopulmonary Resuscitation then Veno-Arterial Extracorporeal Membrane Oxygenation.

Acute myocarditis is one of the common complications of coronavirus disease 2019 (COVID-19) with a relatively high case fatality. Here reported is a fulminant case of a 42-year-old previously healthy woman with cardiogenic shock and refractory cardiac arrest due to COVID-19-induced myocarditis who received veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) after 120 minutes of cardiopulmonary resuscitation (CPR). This is the first adult case of cardiac arrest due to COVID-19-induced myocarditis supported by ECMO that fully recovered with normal neurological functions. The success of the treatment course with full recovery emphasized the potential role of ECMO in treating these patients.

Severe COVID-19-associated myocarditis with cardiogenic shock - management with assist devices - a case report & review.

BACKGROUND: Primary viral myocarditis associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection is a rare diagnosis. CASE PRESENTATION: We report the case of an unvaccinated, healthy patient with cardiogenic shock in the context of a COVID-19-associated myocarditis and therapy with simultaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and percutaneous left ventricular decompression therapy with an Impella. The aim of this review is to provide an overview of therapeutic options for patients with COVID-19-associated myocarditis. CONCLUSIONS: The majority of patients required a combination of two assist devices to achieve sufficient cardiac output until recovery of left ventricular ejection fraction. Due to the rapid onset of this fulminant cardiogenic shock immediate invasive bridging therapy in a specialized center was lifesaving.